The long-term objective of the proposed research is to further understand some of the mechanisms that may be important in controlling the kidney's excretion of sodium. The factor to be investigated in this particular study is endogenous nitric oxide (NO) or endothelial-derived relaxing factor (EDRF). Recent research in this field has shown that NO may be importantly involved in control of blood pressure and body fluid homeostasis. The aims of the present experiments are two-fold. The first is to determine if basal renal function and the increase in excretion caused by volume expansion are altered by blockade of NO synthesis. In addition to measuring various parameters of renal function, the effects of NO synthesis blockade on plasma levels of a number of hormones that can affect the kidney and blood pressure will also be assessed. These will include arginine vasopressin, atrial natriuretic peptide, endothelin, plasma renin activity, angiotension II and epinephrine and norepinephrine. The second aim of these experiments is to investigate the above issues using a new, innovative approach to whole animal studies in fluid-electrolyte physiology. This is a technique in which body sodium and the animal's weight are maintained constant by continuous servo-controlled replacement of urinary sodium and volume losses, and thus the fluid-electrolyte status of the animal is in a steady state condition. Because of this, it will be possible to investigate the renal and hormonal effects of NO in a more accurate and separate fashion than in most whole animal preparations. The results obtained will provide new information about the possible importance of NO in controlling renal excretion and may suggest mechanisms which may be involved or malfunctioning in clinical conditions of body fluid imbalance. My learning this technique will also allow me to later incorporate it into my own research program. A second visit to the sponsor's laboratory is requested to help with any problems encountered with the latter and, if needed, to perform any additional experiments related to the above proposed research.